A Randomized, Controlled Trial of Ganaxolone in Patients With Infantile Spasms

• ClinicalTrials.gov Identifier: NCT00441896
• Recruitment Status: Completed
• First Posted: March 1, 2007
• Last Update Posted: November 17, 2020
• Sponsor: Marinus Pharmaceuticals
• Information provided by (Responsible Party): Marinus Pharmaceuticals

Study Description

Brief Summary:

The study is a two period (8-10 days/period), incomplete cross-over in which successive cohorts of 9 subjects are randomized, in a 2:1 ratio, to 1 of 2 sequences, A and B. In each cohort, Sequence A, comprised of 6 subjects, receives ascending doses of ganaxolone during period 1 and ganaxolone (at the maximal dose attained in period 1) and ascending doses of placebo during period 2. Sequence B, comprised of 3 subjects, receives ascending doses of placebo during period 1 and receives the maximum dose of placebo and ascending doses of ganaxolone during period 2. The dosing level in each subsequent cohort will be based upon experience gained from previous cohorts.

Condition or disease	Intervention/treatment	Phase
Infantile Spasms	Drug: Ganaxolone; Other: Placebo	Phase 2

Detailed Description:

Male or female, 4 to 24 months of age (inclusive) with a diagnosis of IS with a 24 hour video EEG (vEEG) recording confirming the diagnosis and previously treated with 3 or fewer antiepileptic drugs (AEDs) are eligible for the study. The subject is able to continue treatment with concomitant AEDs (no more than 2; adrenocorticotropic hormone [ACTH], corticosteroids, felbamate, and vigabatrin are not allowed concomitantly). A ketogenic diet is permitted if it can be maintained for the duration of the study.

There will be a total of three weekly 24-hr video EEGs (baseline, end of weeks 1 and 2 of treatment). Dosing titration begins the day after each video EEG during the inpatient stay. All subjects will be receiving ganaxolone the day after the second video EEG.

A Data Monitoring Board (DMB) will determine whether successive cohorts of subjects can be dosed at an increased dose level; up to a maximum of 6 cohorts.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-blind, Placebo-controlled, Dose-ranging Clinical Study to Evaluate the Safety, Tolerability, and Antiepileptic Activity of Ganaxolone in Treatment of Patients With Infantile Spasms
• Study Start Date: January 2007
• Actual Primary Completion Date: May 2008
• Actual Study Completion Date: May 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: ganaxolone; ganaxolone	Drug: Ganaxolone
Placebo Comparator: non-active drug; placebo	Other: Placebo

Outcome Measures

Primary Outcome Measures :

1. Spasm frequency as measured by a 24-hour vEEG at Visit 5 (Day 9 ±1 day). [ Time Frame: 1 week ]

Secondary Outcome Measures :

1. Spasm frequency after two weeks of treatment, as determined by 24-hour vEEG. [ Time Frame: 2 weeks ]
2. Cessation of hypsarrhythmia, as determined by vEEG. [ Time Frame: 1 week, 2 weeks ]
3. Investigator and caregiver global assessment of seizure severity and response to treatment at Weeks 1 and 2. [ Time Frame: 1 week, 2 weeks ]
4. The number of subjects spasm-free and seizure-free (for at least 24 hours) at Weeks 1 and 2. [ Time Frame: 1 week, 2 weeks ]
5. Responders (≥ 50% decrease in spasm frequency) at Weeks 1 and 2. [ Time Frame: 1 week, 2 weeks ]
6. Reduction of other seizure types at Weeks 1 and 2. Parents/caregivers will maintain a spasm/seizure diary for clinical study subjects. [ Time Frame: 1 week, 2 weeks ]
7. Investigators and caregivers assessment of the presence and absence of spasms in each subject following treatment. [ Time Frame: 1 week, 2 weeks ]
8. Developmental assessment. [ Time Frame: 2 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 4 Months to 24 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Be diagnosed with IS (regardless of etiology- except for a progressive neurologic illness). Diagnostic Criteria: Seizures consisting of single or repetitive short muscular contractions leading to flexion or extension. Spasms may be characterized as tonic or myoclonic contractions, may occur singly or in clusters, and typically occur bilaterally and symmetrically. The EEG pattern must be consistent with the diagnosis of IS (hypsarrhythmia, modified hypsarrhythmia, multifocal spike wave discharges, etc).
• Have a vEEG recording confirming the diagnosis of IS.
• Have had a magnetic resonance imaging (MRI) performed to determine any possible causes of IS.
• Have been previously treated with 3 or fewer AEDs.

• If being treated with concomitant AEDs

  • Current AEDs have been at a constant daily dose for at least 2 weeks; Note: Subjects with minor dose adjustments may be allowed to enter the study after shorter periods after detailed discussion with the medical monitor.
  • Have a stable clinical response/plateau for at least 2 weeks
  • Are able to continue treatment with no more than 2 concomitant AEDs (ACTH, corticosteroids, felbamate, and vigabatrin are not allowed concomitantly).
  • A ketogenic diet is permitted if it can be maintained for the duration of the study.
• Be a male or female, 4 to 24 months of age (inclusive)
• Have a Parent/Guardian who is properly informed of the nature and risks of the clinical study, who is willing and capable of complying with all clinical study procedures, and has given informed consent in writing prior to entering the clinical study
• Be able to participate for the full term of the clinical study.

Exclusion Criteria:

• Treatment with corticosteroids, ACTH, vigabatrin, felbamate, or any AED not approved by Regulatory Agencies, 2 weeks prior to randomization.
• Treatment with more than two AEDs at baseline.
• Have an active CNS infection, demyelinating disease, degenerative neurological disease, or CNS disease deemed progressive (with the exception of tuberous sclerosis) as evaluated by brain imaging (MRI).
• Have any disease or condition (medical or surgical) at screening that might compromise the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, or hepatic systems; or other conditions that might interfere with the absorption, distribution, metabolism, or excretion of the investigational product, or would place the subject at increased risk.
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin greater than four times the upper limit of normal (ULN) or clinical laboratory value deemed clinically significant by the Investigator.
• History of recurrent status epilepticus.
• Have been exposed to any other investigational drug within 30 days prior to randomization.

Contacts and Locations

Locations

United States, California

Children's Hospital of Los Angeles

Los Angeles, California, United States, 90027

Mattel Children's Hospital at UCLA

Los Angeles, California, United States, 90095

United States, District of Columbia

Children's National Medical Center

Washington, District of Columbia, United States, 20010

United States, Florida

Miami Children's Hospital, The Brain Institute

Miami, Florida, United States, 33155

Child Neurology Care Center of Northwest Florida

Pensacola, Florida, United States, 32504

Child Neurology Center of Northwest Florida

Pensacola, Florida, United States

United States, Illinois

University of Chicago Comer Children's Hospital

Chicago, Illinois, United States, 60637

United States, Minnesota

Minnesota Epilepsy Group, P.A.

Saint Paul, Minnesota, United States, 55102

United States, New York

Montefiore Medical Center- Albert Einstein College of Medicine

Bronx, New York, United States, 10467

United States, Tennessee

Le Bonheur Children's Medical Center

Memphis, Tennessee, United States, 38105

United States, Texas

Dallas Pediatric Neurology Associates

Dallas, Texas, United States, 75230

Texas Children's Hospital

Houston, Texas, United States, 77030

United States, Virginia

Virginia Commonwealth University Health System

Richmond, Virginia, United States, 23298

United States, Washington

Children's Hospital and Regional Medical Center

Seattle, Washington, United States, 98105

United States, Wisconsin

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States, 53201

Sponsors and Collaborators

Marinus Pharmaceuticals

Investigators

• Study Director: Joseph Hulihan, MD; Marinus Pharmaceuticals, Inc.

More Information

Additional Information:

information about ganaxolone 

• Responsible Party: Marinus Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00441896
• Other Study ID Numbers: 1042-0500
• First Posted: March 1, 2007
• Last Update Posted: November 17, 2020
• Last Verified: November 2020

Keywords provided by Marinus Pharmaceuticals:

infantile spasms; anticonvulsant; pediatric epilepsy; West Syndrome; epileptic spasms

Additional relevant MeSH terms:

Muscle Cramp; Spasm; Spasms, Infantile; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Muscular Diseases; Musculoskeletal Diseases; Epilepsy, Generalized; Epilepsy; Brain Diseases; Central Nervous System Diseases; Epileptic Syndromes; Ganaxolone; Neurosteroids; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; GABA Modulators; GABA Agents